Vasopressie-induced sensitization: involvement of neurohypophyseal peptide receptors

Abstract Rats pretreated with an intracerebroventricular (i.c.v.) injection of 10 pmol of vasopressin or vasoprcssin analogs, including deamino- d -vasopressin, [pGlu 1 ,Cyt 6 ]vasopressin, [pGlu-Asn-Cys(Cys)]Pro-Leu-Gly-NH 2 , des-Gly-NH 9 2 -vasopressin, Pro-Leu-Gly-NH 2 , Pro-Arg-Gly-NH 2 , became markedly hyper-responsive to the motor effects, 24 h later, to a subsequent challenge dose of vasopressin, but not vasopressin-related peptides. A vasopressin V 1 receptor antagonist, [d(CH 2 ) 1 5 , Tyr(Me) 2 ]vasopressin. but not the vasopressin V 2 receptor antagonist, [d(CH 2 ) 1 5 , Tyr(Et) 2 ,Val 4 ]vasopressin, or a more selective vasopressin V 2 receptor antagonist, [d(CH 2 ) 1 5 , d -Ile 2 ,Ile 4 ]vasopressin, or the oxytocin receptor antagonist, [d(CH 2 ) 1 5 , Tyr(Me) 2 , Thr 4 ,Orn 8 , Tyr-NH 9 2 ]vasotocin ([d(CH 2 ) 1 5 ,Tyr(Me) 2 ,Thr 4 ,Tyr-NH 9 2 ]OVT), blocked vasopressin and vasopressin analog-induced sensitization. Furthermore, both vasopressin V 2 receptor antagonists were found to sensitize the brain to a subsequent vasopressin injection. This vasopressin V 2 receptor antagonist-induced sensitization was also blocked by the vasopressin V 1 receptor antagonist. Next. we wanted to determine if this sensitization process could involve the release of endogenous vasopressin in the brain as reflected in an amplification of vasopressin mRNA expression. However pretreatment of rats with an i.c.v. vasopressin injection was not associated with an increase in vasopressin mRNA expression in the bed nucleus of the stria terminalis, medial amygdala or the paraventricular nucleus of the hypothalamus when measured 0, 1, 3, 7, 12, or 24 h after the first vasopressin injection. As many vasopressin analogs can induce sensitization, we suggest that a novel type of receptor may be involved in the sensitization process.